177Lu-PSMA vs. cabazitaxel in patients with castration-resistant prostate cancer: Real-world efficacy and safety data from the ARON-3 study

Background: Radioligand therapy with [177Lu]Lutetium-177-PSMA-617 (177Lu-PSMA) was recently introduced in clinical practice in the US, Latin America and in most European countries for progressive, metastatic castration-resistant prostate cancer (mCRPC). However, multicenter real-world data on cancer-control outcomes are scant. Methods: Real-word data from the ARON-3 collaboration in progressive mCRPC patients treated with 177Lu-PSMA vs. cabazitaxel were collected. A retrospective analysis was performed, including overall survival (OS), progression free survival (PFS), time to treatment failure (TTF) and PSA50/90 rates. Results: Data from 285 (50.1 %) patients receiving 177Lu-PSMA vs. 283 (49.9 %) cabazitaxel after one or two lines of ARPI and Docetaxel were analyzed. PSA50 and PSA90 rates were higher, and TTF and OS were significantly longer in 177Lu-PSMA patients, even after multivariable adjustment (p ≤ 0.01). This effect held true for most subgroups such as age < 70 and ≥ 70 years, ECOG 0-1, distant lymph nodes and one vs. two lines of prior ARPI. Incidence of grade 3-4 adverse events were comparable between both treatments (37 % vs. 43 % for 177Lu-PSMA vs. cabazitaxel cohort p = 0.5) but differed according to the type of adverse events. Sensitivity analyses with cross-over adjustment showed similar effects. Conclusions: Analyzing the currently largest real-world cohort comparing 177Lu-PSMA vs. cabazitaxel, we provided robust information of 177Lu-PSMA being at least equally effective or possibly even superior to cabazitaxel regarding cancer-control outcomes with reasonable side effects.